In nature, organisms of the same species usually differ from each other in some aspects, e.g., their appearance. The differences are genetically determined and are referred to as polymorphism. Genetic polymorphism is the occurrence in a population of two or more genetically determined alternative phenotypes due to different alleles. Polymorphism can be observed at the level of the whole individual (phenotype), in variant forms of proteins and blood group substances (biochemical polymorphism), morphological features of chromosomes (chromosomal polymorphism) or at the level of DNA in differences of nucleotides (DNA polymorphism).
Polymorphism also plays a role in determining differences in an individual's response to drugs. Pharmacogenetics and pharmacogenomics are multidisciplinary research efforts to study the relationship between genotype, gene expression profiles, and phenotype, as expressed in variability between individuals in response to or toxicity from drugs. Indeed, it is now known that cancer chemotherapy is limited by the predisposition of specific populations to drug toxicity or poor drug response.
Although considerable research correlating gene expression and/or polymorphisms has been reported, much work remains to be done. This disclosure supplements the existing body of knowledge and provides related advantages as well.
Regorafenib (BAY 73-4506 and trade-named Stivarga®) is an oral multi-kinase inhibitor with known targeted activity against (VEGFR)-1,-2, and -3, FGFR-1, PDFR-α/Φ and ret, c-Kit, raf-1 kinases. It has been approved for treatment for metastatic colorectal cancer mCRC) and locally advanced gastrointestinal stromal cancer (GIST), with treatment for other types of tumors being explored.